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However, the regulation of this transition during normal and impaired healing remains to be elucidated. In our studies, the switch in macrophage phenotypes during skin wound healing was associated with up\u2010regulation of the peroxisome proliferator\u2010activated receptor (\n                    <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\n                    )\u03b3 and its downstream targets, along with increased mitochondrial content. In the setting of diabetes, up\u2010regulation of\n                    <jats:styled-content style=\"fixed-case\">PPAR\u03b3<\/jats:styled-content>\n                    activity was impaired by sustained expression of\n                    <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\n                    \u20101\u03b2 in both mouse and human wounds. In addition, experiments with myeloid\u2010specific\n                    <jats:styled-content style=\"fixed-case\">PPAR\u03b3<\/jats:styled-content>\n                    knockout mice indicated that loss of\n                    <jats:styled-content style=\"fixed-case\">PPAR\u03b3<\/jats:styled-content>\n                    in macrophages is sufficient to prolong wound inflammation and delay healing. Furthermore,\n                    <jats:styled-content style=\"fixed-case\">PPAR\u03b3<\/jats:styled-content>\n                    agonists promoted a healing\u2010associated macrophage phenotype both\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    , even in the diabetic wound environment. Importantly, topical administration of\n                    <jats:styled-content style=\"fixed-case\">PPAR\u03b3<\/jats:styled-content>\n                    agonists improved healing in diabetic mice, suggesting an appealing strategy for down\u2010regulating inflammation and improving the healing of chronic wounds. Copyright \u00a9 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/path.4548","type":"journal-article","created":{"date-parts":[[2015,4,15]],"date-time":"2015-04-15T07:16:14Z","timestamp":1429082174000},"page":"433-444","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":166,"title":["Macrophage PPAR\u03b3 and impaired wound healing in type 2 diabetes"],"prefix":"10.1002","volume":"236","author":[{"given":"Rita E","family":"Mirza","sequence":"first","affiliation":[{"name":"Department of Kinesiology and Nutrition University of Illinois  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milie M","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Nutrition University of Illinois  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret 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